...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A gating mechanism proposed from a simulation of a human α7 nicotinic acetylcholine receptor
【24h】

A gating mechanism proposed from a simulation of a human α7 nicotinic acetylcholine receptor

机译：通过模拟人α7烟碱乙酰胆碱受体提出的门控机制

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The nicotinic acetylcholine receptor is a well characterized ligand-gated ion channel, yet a proper description of the mechanisms involved in gating, opening, closing, ligand binding, and desensi-tization does not exist. Until recently, atomic-resolution structural information on the protein was limited, but with the production of the x-ray crystal structure of the Lymnea stagnalis acetylcholine binding protein and the EM image of the transmembrane domain of the torpedo electric ray nicotinic channel, we were provided with a window to examine the mechanism by which this channel operates. A 15-ns all-atom simulation of a homology model of the homomeric human α7 form of the receptor was conducted in a solvated palmitoyl-2-oleoyl-sn-glycerol-phosphatidylcholine bi-layer and examined in detail. The receptor was unliganded. The structure undergoes a twist-to-close motion that correlates movements of the C loop in the ligand binding domain, via the β10-strand that connects the two, with the 10° rotation and inward movement of two nonadjacent subunits. The Cys loop appears to act as a stator around which the α-helical transmembrane domain can pivot and rotate relative to the rigid β-sheet binding domain. The M2-M3 loop may have a role in controlling the extent or kinetics of these relative movements. All of this motion, along with essential dynamics analysis, is suggestive of the direction of larger motions involved in gating of the channel.
机译：烟碱型乙酰胆碱受体是一个特征明确的配体门控离子通道，但对门控，打开，关闭，配体结合和脱敏的机制尚无适当描述。直到最近，有关该蛋白质的原子分辨率结构信息仍然有限，但是由于产生了Lymnea stagnalis乙酰胆碱结合蛋白的x射线晶体结构以及鱼雷电射线烟碱通道的跨膜结构域的EM图像，提供一个窗口来检查此通道的运行机制。在溶剂化的棕榈酰基-2-油酰基-sn-甘油-磷脂酰胆碱双层中进行受体的同源人α7形式的同源性模型的15 ns全原子模拟，并进行了详细研究。受体是未配体的。该结构经历了从扭曲到闭合的运动，该运动通过连接二者的β10链将配体结合域中C环的运动与两个不相邻亚基的10°旋转和向内运动相关联。 Cys环似乎起着定子的作用，α螺旋跨膜结构域可围绕该定子相对于刚性β-sheet结合结构域枢转和旋转。 M2-M3回路可能在控制这些相对运动的程度或动力学方面起作用。所有这些运动，以及基本的动力学分析，都暗示了通道选通中涉及的较大运动的方向。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号